Abstract: OBJECTIVE To develop a ultra performance liquid chromatography coupled with triple quadrupole mass spectrometry(UPLC-MS/MS) method to determine 8 antidepressants in tranquilizing traditional Chinese medicine and health food. METHODS The analysis was performed by a UPLC-MS/MS system with Waters ACQUITY UPLC BEH C₁₈ (2.1 mm×100 mm, 1.7 µm) column. Multiple-reaction monitoring (MRM) was performed to identify and quantify 8 antidepressants(venlafaxine, citalopram, paroxetine, amitriptyline, trimepramine, fluoxetine, sertraline and clomipramine), which were extracted from samples with methanol. RESULTS Linear calibration curves were obtained with r ≥ 0.995 5. The precision of the method was showed by RSDs (n=6) ranging from 1.5% to 4.6%. The recoveries were determined at three concentration levels and ranged from 88.2% to 103.2%. The ranges of LOQs were from 0.02 to 0.03 µg·L^-1 and the RSDs(n=9) of intra-day precision and inter-day precision were from 1.1% to 3.8% and from 1.4% to 3.7%, respectively. CONCLUSION The method is specific, simple and rapid to detect 8 antidepressants in tranquilizing traditional Chinese medicine and health food.